Impact of bridging therapy (BT) on outcome of relapsed refractory multiple myeloma (RRMM) with Ide-cel CAR T-cell therapy: Real-world experience from the US myeloma CAR T consortium.
Authors: Aimaz Afrough, Hamza Hashmi, Doris K. Hansen, Surbhi Sidana, Chul Ahn, Danai Dima, Ciara L. Freeman, Omar Alexis Castaneda Puglianini, Mehmet H. Kocoglu, Shebli Atrash, Peter M. Voorhees, Leyla Shune, Gary Simmons, Douglas W. Sborov, Christopher J. Ferreri, Charlotte Burton Wagner, Krina K. Patel, Jack Khouri, Larry D. Anderson, Jr, Yi Lin
Journal: Journal of Clinical Oncology (2023)

8013 Background: Ide-cel is an FDA-approved treatment for RRMM patients (pts). However, there is limited data on how BT for disease control during its manufacturing process affects clinical outcomes. Methods: Eleven US academic centers contributed data to this analysis without involvement from the manufacturer. By 5/1/2022, 235 pts had undergone leukapheresis, with 214 infused with a median follow up of 9 months (mos). BT was given between leukapheresis and CAR-T infusion. Results: In this analysis, 79% of pts (n = 170) received BT, which included alkylator-based in 35.5%, steroid and/or IMiD/Ab combos (IMiD combos) in 14%, PI combinations (PI combos) in 12%, and selinexor in 10%. BT recipients had higher ECOG PS 2-4, R-ISS 2-3, ferritin, and CRP before lymphodepleting (LD) chemo, however, no difference among BT subgroups. No difference in prior lines of therapy or penta-refractory between BT and No BT (NBT) groups or BT subgroups. Median cycle of the BT was 1 (1-7), with overall response rate (ORR) of 12%, with no difference among BT subgroups. Incidence and severity of CRS and ICANs were comparable in BT and NBT. However, pts who received BT had a longer median hospital stay compared to NBT, particularly in the alkylator/selinexor subgroups. There were no significant difference in cytopenias at day 90 post CAR-T between the BT and NBT or BT subgroups. For the 73% (n = 157) evaluable for day 90 response, there was no difference in the complete or ORR between the BT and NBT groups (41% vs. 52%; p = .2 and 84% vs. 87.5%, p = .8, respectively). Median PFS was worse at 8.1 mos in BT vs 11.5 mos in NBT (p = .03). Among BT subgroups, PFS was the longest with IMiD combos with median PFS not reached (NR), comparable to NBT, and was significantly longer than all other BT subgroups (p = 0.01). The median OS was 13.8 mos with BT and NR in NBT (p = .002). In BT subgroup analysis, alkylators had a shorter OS, although, this was not significant (p = .06). There was no significant difference in PFS and OS in relationship to response to BT (p = .6 and p = .9, respectively). Conclusions: Pts without BT had longer PFS and OS post ide-cel, likely reflective of less aggressive disease. Those who received BT with steroid/IMiD and Ab combos had similar PFS as NBT. However, BT choice is complicated by disease severity and should be evaluated per patient circumstances. Patient's characteristics and outcomes based on BT. BT Type of BT Yes(N = 170) No(N = 44) P Alkylator(N = 76) IMiD combos(N = 30) PI combos(N = 25) Selinexor(N = 21) P Median Age, yrs 63 65 .4 63 63.5 63 66 .8 ECOG > 1 21% 2% .002 24% 13% 13% 19% .5 EMD 47% 36% .2 54% 27% 48% 57% .052 R-ISS 2- 3 82% 55% .002 82% 95% 90% 79% .4 High-risk cytogenetic 36% 19% .07 39% 38% 37.5% 31.5% .9 Ferritin > 300 ng/mL prior LD 59% 32% .001 63% 50% 52% 62% .5 CRP > 5 mg/L prior LD 25% 9% .02 30% 20% 32% 10% .1 Median hospital stay, days 10 8 < .001 10.5 9 9 11 .6 Median PFS, mos 8.1 11.5 .03 6.9 NR 6.4 9.7 .01